There are a lot of games out there that assume that players will use WASD as their keys to move the player (ie. most flash games). I don't use WASD as my player control when using keyboard and mouse.

I tend to use a AERG (Left-Up-Down-Right) control scheme, due to mainly the size of my hand and WASD feeling too cramped. Plus playing for small periods of time (> 30 min) on WASD makes my hand hurt. The problem that I have is that a lot of the Crouch/Dodge/Target/Run keys are bound to the Left-Ctrl/Alt/Shift which I have a problem using effectively with this layout. I tend to rebind them around my left index finger (on the G). I find that it is sometimes difficult to play in this manner as I don't have a spare finger for extra key presses and sometimes multiple keys are required to be pressed at the same time.

I don't really want to use a controller, and I need something that doesn't put strain on my hands. Are there any improvements/layouts that I could use to reduce repetitive stress and still allow optimal control?

5 Answers
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There are of course some game specific pads, there are also universal gaming keypads, like Razer Nostromo or Logitech G13. On both of them movement (i.e. equivalent of WSAD) can actually be done with just the thumb. I'm not sure how useful is that, but it's definitively different than WSAD.

It really depends on keyboard,standard straight keyboards will have you fingers cramped pretty much anywhere(with only 3 fingers used to control movement)...but the keyboards that are curved tend to have wider keys around FTH some of them are almost 2keys wide and it will give you some extra space.

There are also keyboards developed for certain games (WoW,CoD keyboard...) they have additional keys that are less dense than standard keys...if you manage to bind them as movement keys(or exchange them standard letters on drivers) it could work.

A buddy of mine uses an odd configuration that he loves: It basically involves the forward movement being the Left Mouse button, A for Left and F for Right. Right click for Fire, and then I believe W as a toggle for alt fire. E for crouch and Space for jump. This was his TF2 setup.

The idea behind it is moving the 'Move Forward' key off the keyboard to free up his left hand requirements. You describe large hands so maybe getting a key you use frequently over to the mouse may help.

I doubt people will try this, but you do have two hands; why not use the other one? Even though I'm right-handed I use the mouse with my left hand and use the right to move around with the keypad, which is far more comfortable than the cramped WASD configuration.

What about shifting it up one more row, using Q34T instead of AERG? This would put your thumb higher up, possibly in range of the BNM-Space cluster.

Personally, I have a Nostromo N52 (now available as the Razer Nostromo) that I can hardly game without. Like vartec suggested, you can use the thumbpad to control movement, or use the upper keys for movement and have more keystrokes available for your thumb.